Activation of nucleotide oligomerization domain containing protein 1 induces lipolysis through NF-κB and the lipolytic PKA activation in 3T3-L1 adipocytes

2013 ◽  
Vol 91 (6) ◽  
pp. 428-434 ◽  
Author(s):  
Jaanki S. Purohit ◽  
Pan Hu ◽  
Guoxun Chen ◽  
Jay Whelan ◽  
Naima Moustaid-Moussa ◽  
...  
Keyword(s):  
Hormone Sensitive Lipase ◽  
Dependent Manner ◽  
Camp Production ◽  
Nucleotide Oligomerization ◽  
Hormone Sensitive ◽  
Sirna Knockdown ◽  
Dose Dependent ◽  
Nucleotide Oligomerization Domain ◽  
Oligomerization Domain

Obesity is associated with chronic inflammation. Toll-like receptors (TLR) and NOD-like receptors (NLR) are two families of pattern recognition receptors that play important roles in the immune response and inflammation in adipocytes. Activation of TLR4 has been shown to stimulate lipolysis from adipose tissue or adipocytes. However, effects of activation of nucleotide-oligomerization domain containing protein 1 (NOD1), one of the prominent members of NLRs, on adipocyte lipolysis have not been studied. Here we report that NOD1 activation by the synthetic ligands (Tri-DAP and C12-iEDAP) stimulated lipolysis in 3T3-L1 adipocytes in a time- and dose-dependent manner. C12-iEDAP-induced lipolysis was attenuated with NOD1 siRNA knockdown, demonstrating the specificity of the effects. Moreover, inhibition of the protein kinase A (PKA)/hormone sensitive lipase (HSL) and NF-κB pathways by the pharmacological inhibitors attenuated the lipolytic effects of C12-iEDAP. Furthermore, we show NOD1 activation induced PKA activation independent of cAMP production and inhibition of NF-κB pathways attenuated phosphorylation of selected PKA lipolytic targets (phosphorylation of Perilipin Ser 517 and HSL Ser 563). Taken together, our results demonstrate a novel role of NOD1 activation, via NF-κB/PKA lipolytic activation, in inducing lipolysis in adipocytes and suggest that NOD1 activation may contribute to dyslipidemia in obesity.

scholarly journals Effect of Gambisan on the Inhibition of Adipogenesis in 3T3-L1 Adipocytes

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Jung Won Kang ◽  
Dongwoo Nam ◽  
Kun Hyung Kim ◽  
Jeong-Eun Huh ◽  
Jae-Dong Lee
Keyword(s):  
Dna Content ◽  
Hormone Sensitive Lipase ◽  
Dependent Manner ◽  
Rt Pcr ◽  
Hormone Sensitive ◽  
Ldh Assay ◽  
Dose Dependent ◽  
Oil Red O Staining ◽  
Oil Red O

This study was conducted to explore the antiadipogenic effect and possible mechanism of Gambisan on 3T3-L1 cells. For quality control, Gambisan was standardized by HPLC and the standard compounds ephedrine, epigallocatechin-3-gallate, and caffeine were screened. Cultured 3T3-L1 cells that had been induced to differentiate were treated with various concentrations of Gambisan or its major component extracts (Ephedra intermediaSchrenk,Atractylodes lanceaDC., andThea sinensisL.) for 72 hours for MTT assay to determine cell viability or 10 days for LDH assay, triglyceride assay, DNA content measurement, Oil red O staining, RT-PCR, and western blot. Gambisan significantly inhibited adipogenesis in 3T3-L1 cells by reducing triglyceride contents and lipid accumulation in a dose-dependent manner without obvious cytotoxicity. Viability and DNA content in 3T3-L1 cells treated with Gambisan were significantly higher than cells treated with the major component extracts at every concentration. The anti-adipogenic effects of Gambisan appeared to be mediated by a significant downregulation of the expression of lipoprotein lipase mRNA and PPARγ, C/EBPα, and SREBP-1 protein apart from the expression of hormone-sensitive lipase. Gambisan could act as a possible therapeutic agent for obesity. However, further studies includingin vivoassays and clinical trials are needed to confirm the efficacy, safety and mechanisms of the antiobesity effects of Gambisan.

scholarly journals Nonhematopoietic Cells Control the Outcome of Infection with Listeria monocytogenes in a Nucleotide Oligomerization Domain 1-Dependent Manner

2009 ◽  
Vol 77 (7) ◽  
pp. 2908-2918 ◽  
Author(s):  
Ahmed Mosa ◽  
Christian Trumstedt ◽  
Emma Eriksson ◽  
Oliver Soehnlein ◽  
Frank Heuts ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Listeria Monocytogenes ◽  
Bacterial Load ◽  
Dependent Manner ◽  
Inflammatory Monocytes ◽  
Defensive Role ◽  
Nucleotide Oligomerization ◽  
Increased Susceptibility ◽  
Nucleotide Oligomerization Domain ◽  
Oligomerization Domain

ABSTRACT We analyzed the defensive role of the cytosolic innate recognition receptor nucleotide oligomerization domain 1 (NOD1) during infection with Listeria monocytogenes. Mice lacking NOD1 showed increased susceptibility to systemic intraperitoneal and intravenous infection with high or low doses of L. monocytogenes, as measured by the bacterial load and survival. NOD1 also controlled dissemination of L. monocytogenes into the brain. The increased susceptibility to reinfection of NOD1−/− mice was not associated with impaired triggering of listeria-specific T cells, and similar levels of costimulatory molecules or activation of dendritic cells was observed. Higher numbers of F480+ Gr1+ inflammatory monocytes and lower numbers of F480− Gr1+ neutrophils were recruited into the peritoneum of infected WT mice than into the peritoneum of infected NOD1−/− mice. We determined that nonhematopoietic cells accounted for NOD1-mediated resistance to L. monocytogenes in bone marrow radiation chimeras. The levels of NOD1 mRNA in fibroblasts and bone marrow-derived macrophages (BMM) were upregulated after infection with L. monocytogenes or stimulation with different Toll-like receptor ligands. NOD1−/− BMM, astrocytes, and fibroblasts all showed enhanced intracellular growth of L monocytogenes compared to WT controls. Gamma interferon-mediated nitric oxide production and inhibition of L. monocytogenes growth were hampered in NOD1−/− BMM. Thus, NOD1 confers nonhematopoietic cell-mediated resistance to infection with L. monocytogenes and controls intracellular bacterial growth in different cell populations in vitro.

scholarly journals Crotonis Fructusand Its Constituent, Croton Oil, Stimulate Lipolysis in OP9 Adipocytes

2014 ◽  
Vol 2014 ◽  
pp. 1-5
Author(s):  
Mi-Seong Kim ◽  
Ha-Rim Kim ◽  
Hong-Seob So ◽  
Young-Rae Lee ◽  
Hyoung-Chul Moon ◽  
...  
Keyword(s):  
Positive Control ◽  
Hormone Sensitive Lipase ◽  
Dependent Manner ◽  
Glycerol Release ◽  
Croton Oil ◽  
Croton Tiglium ◽  
Hormone Sensitive ◽  
Main Component ◽  
Culture Supernatants ◽  
Dose Dependent

Introduction. Crotonis fructus (CF) is the mature fruit ofCroton tigliumL. and has been used for the treatment of gastrointestinal disturbance in Asia. It is well known that the main component of CF is croton oil (CO). The present study is to investigate the effects of CF extracts (CFE) and CO on lipolysis in OP9 adipocytes.Methods. Glycerol release to the culture supernatants was used as a marker of adipocyte lipolysis.Results. Treatment with various concentrations of CFE and CO stimulates glycerol release in a dose-dependent manner. The increase in glycerol release by CFE is more potent than isoproterenol, which is aβ-adrenergic agonist as a positive control in our system. The increased lipolysis by CFE and CO was accompanied by an increase of phosphorylated hormone sensitive lipase (pHSL) but not nonphosphorylated HSL protein and mRNA. Pretreatment with H89, which is a protein kinase A inhibitor, significantly abolished the CFE- and CO-induced glycerol release in OP9 adipocytes. These results suggest that CFE and CO may be a candidate for the development of a lipolysis-stimulating agent in adipocytes.

scholarly journals Acetylation of Cavin-1 Promotes Lipolysis in White Adipose Tissue

2017 ◽  
Vol 37 (16) ◽  
Author(s):  
Shui-Rong Zhou ◽  
Liang Guo ◽  
Xu Wang ◽  
Yang Liu ◽  
Wan-Qiu Peng ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Molecular Mechanisms ◽  
Hormone Sensitive Lipase ◽  
Dependent Manner ◽  
Nutritional Regulation ◽  
Fat Mobilization ◽  
Hormone Sensitive ◽  
Shed Light

ABSTRACT White adipose tissue (WAT) serves as a reversible energy storage depot in the form of lipids in response to nutritional status. Cavin-1, an essential component in the biogenesis of caveolae, is a positive regulator of lipolysis in adipocytes. However, molecular mechanisms of cavin-1 in the modulation of lipolysis remain poorly understood. Here, we showed that cavin-1 was acetylated at lysines 291, 293, and 298 (3K), which were under nutritional regulation in WAT. We further identified GCN5 as the acetyltransferase and Sirt1 as the deacetylase of cavin-1. Acetylation-mimetic 3Q mutants of cavin-1 augmented fat mobilization in 3T3-L1 adipocytes and zebrafish. Mechanistically, acetylated cavin-1 preferentially interacted with hormone-sensitive lipase and recruited it to the caveolae, thereby promoting lipolysis. Our findings shed light on the essential role of cavin-1 in regulating lipolysis in an acetylation-dependent manner in WAT.

Of mice and women: the β3-adrenergic receptor leptin and obesity

1996 ◽  
Vol 74 (5) ◽  
pp. 615-622 ◽  
Author(s):  
Nicole Bégin-Heick
Keyword(s):  
Adipose Tissue ◽  
G Proteins ◽  
Adrenergic Receptor ◽  
Metabolic Response ◽  
Human Adipose Tissue ◽  
Hormone Sensitive Lipase ◽  
Camp Production ◽  
Ob Gene ◽  
Hormone Sensitive

The metabolic response of adipose tissue to stimuli leading to lipid mobilization is important in determining the direction of metabolism and the degree to which adipose tissue can store lipids and release fatty acids in times of need. The lipolytic machinery is controlled by the activity of hormone-sensitive lipase, which in turn is controlled by the cellular levels of cAMP. The production of cAMP is abnormal in the adipose tissue of some animal models of obesity. In the ob/ob mouse, the defective cAMP production has been associated with deficient levels of some of the isoforms of the guanine nucleotide transducing G-proteins and also with the low expression and functionality of the β3-adrenergic receptor (β3-AR). The recent discovery of the ob gene product leptin calls into question the role of the ob gene in the regulation of the cAMP cascade in adipose tissue. The importance of the β3-AR and leptin in regulating human adipose tissue metabolism remains to be clarified.Key words: ob gene, lipolysis, adenylyl cyclase, G-proteins, obesity, adipose tissue, beta-adrenergic receptor.

Amelioration of Carbon Tetrachloride-Induced Liver Injury by Citrus Leaf Extract

2019 ◽  
Vol 17 (4) ◽  
pp. 426-431
Author(s):  
Jin Xuezhu ◽  
Li Jitong ◽  
Nie Leigang ◽  
Xue Junlai
Keyword(s):  
Carbon Tetrachloride ◽  
Leaf Extract ◽  
Hepatic Injury ◽  
The Body ◽  
Dependent Manner ◽  
Weight Changes ◽  
Citrus Leaf ◽  
Dose Dependent ◽  
And Oxidative Stress

The main purpose of this study is to investigate the role of citrus leaf extract in carbon tetrachloride-induced hepatic injury and its potential molecular mechanism. Carbon tetrachloride was used to construct hepatic injury animal model. To this end, rats were randomly divided into 4 groups: control, carbon tetrachloride-treated, and two carbon tetrachloride + citrus leaf extract-treated groups. The results show that citrus leaf extract treatment significantly reversed the effects of carbon tetrachloride on the body weight changes and liver index. Besides, treatment with citrus leaf extract also reduced the levels of serum liver enzymes and oxidative stress in a dose-dependent manner. H&E staining and western blotting suggested that citrus leaf extract could repair liver histological damage by regulating AMPK and Nrf-2.

scholarly journals VEGF Mediates Retinal Müller Cell Viability and Neuroprotection through BDNF in Diabetes

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 712
Author(s):  
Yun-Zheng Le ◽  
Bei Xu ◽  
Ana J. Chucair-Elliott ◽  
Huiru Zhang ◽  
Meili Zhu
Keyword(s):  
Specific Protein ◽  
Müller Cell ◽  
Dependent Manner ◽  
Vascular Abnormalities ◽  
Extracellular Signal ◽  
Muller Cell ◽  
Protein Kinase Akt ◽  
Sirna Knockdown ◽  
Endothelial Growth Factor ◽  
Dose Dependent

To investigate the mechanism of vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF) in Müller cell (MC) viability and neuroprotection in diabetic retinopathy (DR), we examined the role of VEGF in MC viability and BDNF production, and the effect of BDNF on MC viability under diabetic conditions. Mouse primary MCs and cells of a rat MC line, rMC1, were used in investigating MC viability and BDNF production under diabetic conditions. VEGF-stimulated BDNF production was confirmed in mice. The mechanism of BDNF-mediated MC viability was examined using siRNA knockdown. Under diabetic conditions, recombinant VEGF (rVEGF) stimulated MC viability and BDNF production in a dose-dependent manner. rBDNF also supported MC viability in a dose-dependent manner. Targeting BDNF receptor tropomyosin receptor kinase B (TRK-B) with siRNA knockdown substantially downregulated the activated (phosphorylated) form of serine/threonine-specific protein kinase (AKT) and extracellular signal-regulated kinase (ERK), classical survival and proliferation mediators. Finally, the loss of MC viability in TrkB siRNA transfected cells under diabetic conditions was rescued by rBDNF. Our results provide direct evidence that VEGF is a positive regulator for BDNF production in diabetes for the first time. This information is essential for developing BDNF-mediated neuroprotection in DR and hypoxic retinal diseases, and for improving anti-VEGF treatment for these blood–retina barrier disorders, in which VEGF is a major therapeutic target for vascular abnormalities.

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